Immune reactions to varicella zoster (VZ) virus are being studied. Our hypothesis is that cellular immunity (CMI) to VZ virus is important in recovery from VZ infections and also in preventing symptoms when reactivation of virus occurs. The first aspect of this study is to delineate normal CMI responses to VZ virus. Thus far we have demonstrated T lymphocyte and macrophage (T/M) CMI, and antibody dependent cellular cytotoxicity (ADCC). Both these reactions cause inactivation of VZ virus in vitro. VZ CMI may also be measured in vitro by lymphoid proliferation (P) in response to VZ antigen. Our studies have shown that T/M CMI develops after varicella and is associated with recovery from VZ infections, and it is depressed in immunocompromised children who are prone to develop clinical zoster. ADCC has been present in all persons tested thus far (including newborns, susceptible adults, and immunocompromised persons). It is of interest that ADCC seems to require fewer effector cells than T/M CMI. Studies of P show that normals have extremely variable responses over six month's time. Studies of VZ IgM antibody in normals also show that this antibody is present in 20 percent of individuals. We therefore propose that reactivation of VZ virus is not an uncommon event but that it is frequently asymptomatic, especially in persons with normal CMI. When CMI is deficient and reactivation occurs, clinical zoster develops. We are now trying to discover what deficiencies in CMI are associated with development of clinical zoster.